ceutics

Qn No.
in Exam
paper
Expected Answer
1.1 Write a critical note on (i) the law governing filtration rate and factors affecting it
(ii) any one continuous-vacuum filter with reference to its construction,
operation, advantage, disadvantage and application.
[P10:4,25,28,26,27,103,104,105]
Filtration is a mechanical or physical operation which is used for the
separation of solids from fluids (liquids or gases) by interposing a
medium through which only the fluid can pass. Oversize solids in the
fluid are retained, but the separation is not complete; s
contaminated with some fluid and filtrate will contain fine particles
(depending on the pore size and filter thickness).
The factors which affect the rate of filtration is expressed by Darcy’ s Law
FACTORS AFFECTING RATE OF FILTRATION
A. Area of surface filter
B. Particle size of the solids to be removed
C. Pore size of the filter media
D. Resistance of the filter cake and filter media
E. Viscosity of the liquid to be filtered
F. Temperature
G. Pressure difference across the filter
1. Properties of the filter medium and filter cake
The resistance of the filter medium and filter cake is denoted by R. The resistance
of filter medium is of less significance in industrial scale than the resistance of
filter cake. The latter increases with time. The rate of f
thickness of the cake increases. When the rate is uneconomically low the
filtration is stopped and the cake is removed mechanically; and the filtration is
resumed.
2
on (i) the law governing filtration rate and factors affecting it
vacuum filter with reference to its construction,
operation, advantage, disadvantage and application.
[P10:4,25,28,26,27,103,104,105] [P10:102, 64-98]
is a mechanical or physical operation which is used for the
fluid are retained, but the separation is not complete; solids will be
(depending on the pore size and filter thickness).
FACTORS AFFECTING RATE OF FILTRATION
Area of surface filter
Particle size of the solids to be removed
Pore size of the filter media
Resistance of the filter cake and filter media
Viscosity of the liquid to be filtered
Pressure difference across the filter
filter medium and filter cake
filter cake. The latter increases with time. The rate of filtration decreases as the
Marks
on (i) the law governing filtration rate and factors affecting it
vacuum filter with reference to its construction,
is a mechanical or physical operation which is used for the
olids will be
iltration decreases as the
8

3
The resistance also depends on the properties of the solids, e.g. particle size,
particle size distribution, particle shape, and compressibility of the solid. In case
of compressible cake the porosity decreases with increasing pressure drop, so
filter aids are incorporated to increase the filtration rate.
2. Area of filter
The rate of filtration can be increased by increasing the area of filtration. This
area can be increased by using larger filters or by using a number of small units
in combination. In rotary filters the filter cake is continuously removed
providing an infinite area of filtration.
3. Pressure drop
Rate of filtration can be increased by increasing the pressure drop across the
filter medium. Pressure drop can be achieved by (i) gravity, (ii) negative
pressure (reduced pressure or under vacuum), (iii) positive pressure and (iv)
centrifugal force.
Gravity: The height of the slurry over the filter medium gives pressure under
gravity. By increasing the height of the slurry the pressure drop can be
increased.
Negative pressure: The pressure below the filter medium can be reduced below
atmospheric pressure by connecting the filtrate receiver to a vacuum pump.
The disadvantage of this method is that the pressure drop can never be increased
above one atmospheric pressure.
The second disadvantage is that under reduced pressure the boiling point of
liquid is lowered and the liquid may boil in the filtrate receiver that may cause
loss of liquid or may damage the vacuum pump.
Positive pressure: The simplest method of raising the pressure difference across
the filter membrane is to increase the pressure to the surface of the slurry.
The advantage is that greater pressure difference can be achieved.
Centrifugal force: The gravitational force can be increased by centrifugal force.
4. Viscosity of liquid
An increase in the viscosity of the liquid will decrease the flow rate. The
viscosity of the liquid can be decreased by raising the temperature of the slurry
or by dilution with a miscible liquid.
5. Thickness of the filter cake
Thickness of the filter cake increases as the filtration progresses. Highly
concentrated slurry is first decanted or strained to reduce the solid content and
then it is filtered (this reduces the cake thickness). In a rotary drum filter cake is
removed continuously so that the cake thickness is minimized.

4
Rotary drum filters consist of a perforated metal drum wrapped with a
filter cloth to act as filter medium
The drum is partially immersed in the tank containing the slurry. The
drum is rotated at a slow speed and vacuum is created. Thus the filtrate
will enter the drum through the filter media and filter cake will be
deposited on the outer surface of the filter medium
The cake can be removed by scrapping with a knife just before the
rotating drum repeats another cycle.
Zone Position operation
Cake Formation
Zone
(Pick-up)
Slurry
trough with
agitator
The drum picks up the slurry as soon as
it comes in contact with the slurry
trough. Cake builds up on the filter cloth
Cake Predrying
Zone
Drainage
filtrate
receiver
Under vacuum the filtrate is received in
filtrate receiver
Cake Washing
Zone
Washing
Wash sprays Water is sprayed on the cake and
simultaneously drainage is taking place.

5
Cake Final Drying
Zone
Drying
Drying or
Hot Air
blower
Under vacuum the filter cake is dried.
Cake Discharge
Zone
Cake removal
Scrapper
knife
Vacuum is reversed i.e. Compressed air is
passed to this zone so that the cake may
be loosen
Dead Zone Cycle repeats
The cake discharge may be carried out by:
(i) Scrapper discharge
In this method a knife is fitted to scrap a small thickness of the pre-coat along
with the cake. But wear and tear on the filter cloth is considerable with scrapper
knife so the cloth is frequently changed.
(ii )String discharge
Numbers of endless strings are placed at about ½ inch pitch over the width of
the drum. The run or this string is extended from an open conveyor system
passing over a discharge and return roller. As compared to scrapper, the wear of
filter cloth is minimized.
(iii)Belt discharge
It makes the filter cloth to pass on the roller and material is discharged on the
first roll and before its passage to the fed trough it is subjected to washing.
Therefore, higher filtration rates may be achieved using belt discharge.
Advantages
(i) It is automatic and continuous; labor cost is low.
(ii) Very high capacity. (iii) Thick slurries containing 15–30% of solids can be
filtered. (iv) Variation of speed of rotation enables the cake thickness to be
controlled. E.g. For solids forming impenetrable cakes thickness is kept constant
within 5 mm. For porous cakes thickness is kept within 100mm.
Disadvantages
(i) Complex design with many moving parts. (ii) Very expensive.
(iii) The cake tends to crack under vacuum, so washing and drying are not
efficient. (iv) As vacuum is applied, it is unsuitable for liquids near boiling point.
(v) Gelatinous or slimy precipitates forming impenetrable cake will not separate
cleanly from cloth.
Application
(i) Collection of calcium carbonate, magnesium carbonate, starch.
(ii) Separation of the mycelium from the fermentation liquor in the manufacture
of antibiotics.

7
Qn No.
in Exam
paper
Expected Answer Marks
1.2 Explain the working principle of a planetary mixer. Discuss how vortex
formation can be controlled in mixing tanks.
[4MY2828.doc, Mixing and homogenization.pdf pg186] [4MY7070.doc]
(i) Planetary motion mixers:
Construction: It consists of a circular base. Inside the container a blade rotates around its own
axis. The axis of the blade again rotates along a shaft. Thus the motion of the blade is similar to
the motion of a planet around the sun. The planet is rotating along its own axis and at the same
time the planet is rotating around the sun. The design of the blade is as shown in the figure.
There is very little clearance between the blade and the wall of the container.
Working: This design allows the revolving blade to handle (mix) a small amount of mass at a
time. Again the blade is moving, carrying the mass to other places. The blade is scraping the
materials those are sticking to the wall of the container.
Application:
1. This sturdy (strong) mixer is used to mix semisolid ointments.
2. To prepare tablets the powder is mixed with binder solutions. During this wet massing step
planetary mixer is used.
Vortexing and its remedies:
If the tangential component is dominant, a vortex forms and may deepen until it reaches the
impeller, and aeration occurs. Due to the high speed of the propellers vortexing and finally
aeration may occur; i.e. air may get entrapped which may be difficult to remove from the
product and the air may encourage oxidation in some cases, causes blade to be less in contact
with liquid, therefore decrease efficiency of mixing.
To avoid vortexing the following strategies can be worked out:
(i) The propeller should be deep into the liquid and [fig (a)]
(ii) Symmetry should be avoided:
(a) propeller shaft may be off-set from the center. [fig (b]
(b) propeller shaft may be mounted at an angle to the vertical wall of the container. [fig
(c)]
(c) the shaft may enter side of the vessel [fig (d)]
(d) or, a vessel other than cylindrical may be used, (N.B. although this is liable to give
4
Container
Blade
Shaft
Fig. Planetary mixer

8
rise to ‘dead spots’ in corners)
(iii) A push-pull type of propeller may be used in which two propellers of opposite pitch are
mounted on the same shaft so that the rotating effects are in opposite directions and cancel
each other. [fig (e)]
(iv) One or more baffles may be used which are usually vertical strips attached to the wall of the
vessel. [fig (f)]
fig (a) fig (b)
fig (c) fig (d)
fig (e)
fig (f)

9
Qn No.
in Exam
paper
2.1 Outline the classification of pharmaceutical dosage forms according to time-
release of drug. Critically compare and contrast key features of routes of
administration that bypass the first pass metabolism.
Drugs are rarely administered in their original pure state. They are converted
into suitable formulations which are called dosage forms. Every dosage form is a
combination of the drug and other non-drug components. The non-dug
components are known as “additives”. The additives are used to give a
particular shape to the formulation, to increase its stability and also to increase
its palatability as well as to give more elegance to the preparation.
According to drug release rate from the tablet :
a- Immediate-release tablet:
The tablet is intended to be released rapidly after administration, or the tablet is
dissolved and administered as solution. It is the most common type and
includes:
1- Disintegrating tablet (conventional or plain tablet)(with or w/o sugar, film
coating)
2- Chewable tablets
3- Effervescent tablets
4- Sublingual and Buccal tablets
5- Lozenges, Troches
Tablets for oral ingestion; Tablets for use in oral cavity; Tablets to prepare
solutions
b- Modified-release tablet:
They have release features based on; time, course or location. They must be
swallowed intact.
(1) Repeat -act ion tablets are layered or compression-coated tablets in
which the outer layer or shel l rapidly disintegrates in the stomach (e.g. ,
Repetabs, Scher ing; Extentabs, Wyeth) . The components of the inner layer
or inner tablet are insoluble in gast ric media but soluble in intestinal media.
(2) Delayed-act ion and enter ic-coated tablets delay the release of a drug
f rom a dosage form. This delay is intended to prevent dest ruct ion of the
drug by gast ric juices, to prevent i rr i tat ion of the stomach l ining by the
drug, or to promote absorpt ion, which is better in the intestine than in the
stomach.
Enter ic-coated tablets are coated and remain intact in the stomach, but yield
thei r ingredients in the intestines (e.g. , Ecotr in, GSk). Enteric-coated tablets are
a form of delayed-act ion tablet . However , not all delayed-action tablets are
enter ic or are intended to produce an enteric ef fect . Agents used to coat these
6

10
tablets include fats, fatty acids, waxes, shel lac, and cellulose acetate phthalate.
(3) Other Sustained- release forms grouped according to their pharmaceutical
mechanism.
a. Coated beads or granules
b. Microencapsulat ion
c. Mat r ix tablets
d. Osmotic systems
e. Ion-exchange resins
f . Complex formation
When a drug is administered by oral route, it undergoes attack by gastric juices
and undergoes first pass metabolism when absorbed into the entero-hepatic
circulation, where a great fraction of it is rendered inactive. Some prodrugs are
converted to the active drug by the same mechanism.
Routes that bypass the first pass metabolism are sublingual, rectal, parentral,
transdermal and respiratory routes.
Sublingual route:
The drug diffuses into the blood, directly through tissues under the tongue in
case of sublingual tablets and through oral mucosa in case of buccal tablets.
Adv: Bypass first pass metabolism, Rapid action achieved
Eg: nitroglycerin sublingual tablet for relief of angina
Rectal route:
Suppositories administered rectally melt and dissolve to provide local action or
achieve systemic absorption.
Adv: Useful when oral administration is inappropriate, as with infants,
debilitated or comatose patients, and patients who have nausea, vomiting, or
gastrointestinal disturbances. Bypass first pass metabolism to some extent
except where upper hemorrhoidal veins are involved.
Dis: Uncertain/unpredictable absorption, local irritation and possible accidental
loss of the medication.
Parentral route:
Preparations injected directly into body tissue through the primary protective
systems of the human body, the skin and mucous membranes must be
exceptionally pure and free from contaminants.
Adv: Immediate action; Dose can be adjusted accurately; useful for unconscious,
uncoorporative patient, for drugs with poor oral absorption.
Dis: require aseptic conditions, pain factor, risk of local irritation, difficulty in
correcting the error.

11
Respiratory route: preparations are inhaled for local action or systemic action.
Advantages: rapid onset of action; bypass the hepatic circulation; avoidance of
degradation in the gastrointestinal tract; lower dosage that minimizes adverse
reactions; simple, convenient and acceptable therapy.
Transdermal route: Preparations applied are absorbed through skin and provide
local and systemic action.
Adv: transdermal delivery systems provide long term systemic delivery.
Eg antianginals, analgesics(Durogesic), contraceptives

12
Qn No.
in Exam
paper
2.2 (i) Which of the following amounts of copper sulphate is required to make
400 mL of an aqueous stock solution, such that, when the stock solution is
diluted 50 times with water, a final solution of 0.1% w/v copper sulphate is
produced?
A 0.2 g B 20.0 g C 0.4 g D 40.0 g E 50.0 g
Final conc.=0.1%w/v
Dilution factor=50
Stock conc.=0.1 x 50 = 5%w/v
100ml stock contains 5g CuSO4
400ml stock contains 20gCuSO4
Ans: B
(ii) You have in your pharmacy a cream containing 0.05% w/w Clobetasone.
You have been requested to use this cream as a base and to add in sufficient
miconazole such that the final concentration of miconazole in the new cream
will be 2.0% w/w. What is the concentration of Clobetasone in the new
cream?
A 0.025% w/w B 0.49% w/w C 0.5% w/w D 0.05% w/w E 0.049%
w/w
0 (100-2) 98
2
100 -(0-2) 2
98part cream + 2part miconazole powder=100part mixture
100g newcream contains 98gcream and 2gmiconazole
0 (0.05-x) 2
X
0.05 (x) 98
12part miconazole powder (containing 0%w/w colbetasone) when added to 988
parts 0.05%w/w colbetasone cream dilutes colbetasone to a final concentration
of X%w/w.
(0.05-x)/x=2/98
98(0.05-x)=2x
4.9-98x=2x
8

13
4.9=100x
X=0.049
New cream contains 0.049%w/w colbetasone.
Ans:E
(iii) Toxic residues are sometimes found in drinking water in industrial areas.
For compound Z, the safe limit for drinking water is 92 ppm. Analytical
results for the amount of compound Z in the drinking water of various
locations are given below. Which ONE of the following locations has
drinking water that is NOT safe to drink?
A Toome: 41.0 micrograms/mL
B Blackhill: 0.3 mg/L
C Drumhowan: 0.0045% w/v
D Magheracloone: 0.00041 g/ml
E Annagassan: 1 in 100 000
Toome: 41 micrograms/mL = 41 mg/1000 mL = 41 g in
1 000 000 mL or 41 ppm
41 ppm < 92 ppm, so the water in Toome is drinkable
Blackhill: 0.3 mg/L = 0.3 mg/1000 mL = 0.3 g/1000 000 mL or
0.3 ppm
0.3 ppm < 92 ppm, so the water in Blackhill is drinkable
Drumhowan: 0.0045% w/v = 0.0045 g/100 mL = 0.045 g/1000 mL =
45.0 g/1000 000 mL or 45 ppm
45 ppm < 92 ppm, so the water in Drumhowan is drinkable
Magheracloone: 0.00041 g/ mL = 0.41 g/1000 mL =
410.0 g/1000 000 mL or 410 ppm
410 ppm > 92 ppm, so the water in Magheracloone is not drinkable
Annagassan: 1 in 100 000 is the same as 10 in 1000 000 or 10 ppm
10 ppm< 92 ppm, so the water in Annagassan is drinkable.
Ans:D
(iv) Match the comments in I) II) III) to the appropriate answer from A to E.
I) The volume of an oral liquid medicine, available as 2 mg drug X/5 mL,
which is required for a 14-day supply for a patient prescribed a dose of 4 mg
drug X three times daily.

14
II) The volume of alcohol 95% v/v needed to produce 1.90 L of 50% v/v.
III) The volume of concentrated peppermint water required to make 16.8 L of
single-strength peppermint water. (Single-strength peppermint water is 1
part concentrate to 39 parts water.)
A 100 mL B 1000 mL C 4200 mL D 420 mL E 4.2 mL
I) D
The patient requires 4 mg drug X three times daily, so needs 12 mg/day. If
the drug is formulated at 2 mg/5 mL, then 6 × 5 mL doses are required per
day. If the patient, therefore, needs 30 mL/day for 14 days, 420 mL are
required. Accordingly, the correct answer is D.
II) B
1.90 L of 50% v/v contains 0.95 L alcohol
95% v/v contains 95 mL alcohol in 100 mL. Therefore, the volume of
alcohol 95% v/v containing 0.95 L alcohol can be calculated as follows:
(0.95/95) × 100 = 1.00 L or 1000 mL.
Accordingly, the correct answer is B.
III)D
For every 40 mL single-strength peppermint water you have 1 mL
concentrate. Therefore in 16.8 L, or 16 800 mL, you have 16 800/40 =
420 mL.
Accordingly, the correct answer is D.

15
Qn No.
in Exam
paper
3.1 Classify extraction methods and compare them. Explain soxhelation with a
diagram. Comment on the merits and demerits of continuous hot percolation.
[P7:15, P7B:1], [P7B:14, P7:16] [P7:29-31, P7B:4-5]
Extraction refers to processes for the isolation of the active ingredients from drug
material. This may be by physical means or by dissolving in a suitable solvent.
-Expression is the physical act of applying pressure to squeeze out oils or juices
from plants. This was normally achieved with a tincture(hydraulic) press
-Cold Methods: Maceration, Percolation and Infusion (used for thermolabile
components)
-Hot Method: Decoction, Hot Continuous Extraction, Distillation
Extraction
method
Time for
extraction
Temperature Characteristics of the active
constituents
Maceration
Percolation
Digestion
Infusion
Decoction
3-7 days
24 hours
Few days
Short period
15 mins
Room temp
Room temp
Moderately high
Cold or boiling
water
Boiling water
• Soluble in the menstruum
• Heat stable / unstable
• Soluble in the menstruum
• Heat stable / unstable
• Heat stable
• Readily soluble
• Water soluble
• Heat stable
Or
8
EXTRACTION PROCESSES
INFUSION DECOCTION MACERATION /
DIGESTION
PERCOLATION
Fresh
Infusion
Concentrated
Infusion
Simple
Maceration
Maceration with
adjustment
Multiple
Maceration
Double
Maceration
Triple
Maceration
Simple
Percolation
Continuous
Hot Percolation
(Soxhlation)
Percolation
Process for
Conc. Preparation
Reserved
Percolation
Modified
Percolation
.

17
soxhelation
Classic techniques for the solvent extraction of active
constituents from medicinal plant matrices are based
on the choice of solvent coupled with the use of heat
or agitation. Existing classic techniques used to
obtain active constituents from plants include:
Soxhlet, hydrodistillation and maceration with an
alcohol-water mixture or other organic solvents.
Soxhlet extraction is a general and well-established
technique, which surpasses in performance other
conventional extraction techniques except for, in
limited fields of application, the extraction of
thermolabile compounds.
In a conventional Soxhlet system, as shown in
Figure above, plant material is placed in a thimble-
holder, which is filled with condensed fresh solvent
from a distillation flask. When the liquid reaches the
overflow level, a siphon aspirates the solution of the
thimble-holder and unloads it back into the
distillation flask, carrying extracted solutes into the
bulk liquid. Solute is left in the fl ask and fresh
solvent passes back into the plant solid bed. The
operation is repeated until complete extraction is
achieved.
This process is used for those drugs
•where the penetration of the menstruum into the
cellular tissues is very slow and
•the solute is not readily soluble into the solvent and
•the quantity of the menstruum is very less.
In such cases Soxhlet extractor is used where small volume of hot menstruum is
passed over the drug time and again to dissolve out the active constituents until
the drug is exhausted. The process is known as Soxhlation.
Apparatus:
i)A round bottom flask in which the menstruum is boiled.
ii)An extraction chamber in which drug is filled, is fitted with side tube and a
siphon.
iii)A reflux condenser.
The size of the drug is reduced.
The drug is packed in a ‘thimble’ made of filter paper which is then placed into
the wider part of the extractor.
[N.B. thimble is used to prevent choking of the lower part of the extractor.]

18
Menstruum is placed in the flask and boiled. The vapor rises through the side
tube to the condenser, where the vapor is condensed and fall on the packed
drug, through which it percolates and extract out the active constituents.
As the volume of menstruum in the extractor increases, the level of liquid in the
siphon also increases till it reaches the maximum point from where it is siphoned
out into the flask.
On further heating the menstruum vaporizes while the dissolved active
constituents remain behind in the flask. The alternate filling and emptying of the
body of the extractor goes on continuously till the drug is exhausted. Thus the
same quantity of menstruum is made to percolate repeatedly, about 14 to 15
times through the drug and the active constituents are collected in the flask.
Merits/Demerits
Despite the economic advantages of solvent extraction, the use of volatile
organic solvents such as hexane, acetone and methanol for processing medicinal
plants has been limited due to environmental considerations. Hot continuous
extraction technology shall always remain the method of choice for high
efficiency, economical extraction and with less capital investment.
Advantages: Disadvantages:
1. The displacement of
transfer equilibrium by
repeatedly bringing fresh
solvent into contact with the
solid matrix.
2. Maintaining a relatively
high extraction temperature
with heat from the distillation
fl ask.
1. Agitation is not possible in the Soxhlet
device.
2. The possibility of thermal decomposition
of the target compounds cannot be ignored
as the extraction usually occurs at the
boiling point of the solvent for a long time.
Chemical constituents of the drug: The
process is unsuitable for thermolabile active
constituents, e.g. enzymes, alkaloids,
anthraquinone derivatives, esters etc
3.Physical character of the drug: If the
physical character of the drug is such that it
would block the Soxhlet apparatus then this
method is not suitable. e.g opium, gum,
resin, orange peel etc.
4.Solvent: Only pure solvents or constant
boiling mixtures (like alcohol-water) can be
used for this purpose.

19
Qn No.
in Exam
paper
3.2 Explain the construction, operation, advantages, disadvantages and applications
of hammer mills. List factors affecting choice of size reduction equipment.
[P8A:28-29] [P8A: 37-38, 16-17].
HAMMER MILL
Method of size reduction: Impact
Construction and working :
Hammer mill consists of a stout
metal casing, enclosing a central
shaft to which four or more
hammers are attached. These are
mounted with swivel joints, so
that the hammers swing out to a
radial position when the shaft is
rotated. The lower part of the
casing consists of screen through
which materials can escape,
when sufficiently size reduced.
The material is collected in a
container placed below the
screen.
The screen can be changed according to the particle size required.
According to the purpose of operation the hammers may be square-faced,
tapered to a cutting form or have a stepped-form.
The interior of the casing may be undulating in shape, instead of smooth
circular form for better impact.
The rotor operates at a speed of 80cycles per second.
Advantages:
(a) It is rapid in action, and is capable of grinding many different types of materials.
(b) The product can be controlled by variation of rotor speed, hammer type and size and
shape of mesh. (c) Operation is continuous. (d) No surface moves against each other so
very little problem of contamination of mill materials.
Disadvantages:
(a) High speed of operation generates heat that may affect thermolabile materials
or drugs containing gum, fat or resin.
(b) The rate of feed should be controlled otherwise the mill may be choked.
(c) Because of high speed of operation, the hammer mill may be damaged if
some foreign materials like stone, metal pieces etc. are present in the feed.
Applications: Powdering of crystals and filter cakes.
8

20
Factors influencing choice of Size Reduction machinery
1. Nature of the raw material: Drugs must be thoroughly dried before they are
subjected to size reduction. Drugs like belladonna, gentian, liquorice and squill
are returned to the drying rooms to the drying rooms after they have been
partially comminuted, as they rapidly absorb absorb moisture from the
atmosphere and as the moisture may not be removed from all parts of the drug
during the initial drying stage. In the case of water insoluble substances, wet
grinding of the material can be done. For the preparation of aqueous dispersions
of drugs this method is very effective since deflocculating agents may be
included to prevent agglomeration of the particles.
Substances that are hygroscopic or volatile or very poisonous or that need-
prolonged trituration are more easily prepared in closed porcelain ball mills.
Fibrous material seed tearing apart of the fibres and this can be achieved in high-
speed impact mills. Substances of a resinous or oily nature shall not be subjected
to heavy pressures or much heat as a pasty mass may result. Hence, a ball mill
will not be suitable and they are better grounded in a micronizer or a hammer
mill. The replacement of air by an inert gas is necessary when grinding readily
oxidizable materials and ball mills and high-speed impact mills are generally
used in this way.
2. Nature of the product: A powdered drug produced in a ball mill differs from
the product in a micronizer or a disintegrator even though both powders may be
screened to the same fineness. Differences exist in the shape of the particles, their
toughness and their internal pore structure. Powder obtained from grinding
mills like ball mill is more compact and less porous than that obtained in high
speed impact mills like a disintegrator. For the grinding of a sterile material
under aseptic conditions, a mill is required that can be easily sterilized and
sealed to prevent contamination during the grinding operation. A batch
operation porcelain ball mill is most suitable for this purpose. When iron and
copper contamination of pharmaceutical products is to be avoided stainless steel
or ceramic material may be used for the surfaces of a mill coming into contact
with the drug.
3. Degree of comminution required: The degree of comminution of materials
varies according to the purpose for which they are required. For the preparation
of galenicals, the size of the vegetable drug powder employed for extraction
varies from coarse to fine powder. Tincture preparation requires bruised to
moderately coarse powders. For percolation, drug powders should not contain a
large proportions of fines to avoid uneven extraction. Coarse to moderately
coarse powder, with a minimum of fine powder, are all most easily obtained by
using high speed mills of the impact type. Materials such as cascara, liquorice,
belladonna leaf and root and ginger are all easily broken down in such mills. The
grindability of different grades of a vegetable drug usually varies and during
comminution the softer portions get size reduced first. Therefore it is sometimes

21
useful to screen out the powdered drug and return the coarser material to the
mill for further size reduction. This prevents continued milling of the softer
portions resulting in formation of too much fines. The same principle is also
applicable to crystalline drugs although they are of uniform composition. The
rate of absorption of sparingly soluble drugs, either through the Gastro-
intestinal tract or when administered parenterally, depends on particle size.
Penicillin in a medium of aluminium monostearte and arachis oil appears to be
most effective when 90 % of the particles are smaller than 5 micrometers. The
relatively insoluble sulphonamides attain their maximum antibacterial activity at
crystal sizes of about 1 micrometer or below. For insufflations the drug should
be smaller than about 5 micrometers.

22
Qn No.
in Exam
paper
3.3 Classify pharmaceutical additives. Comment on the relation between their
purity and their quality with examples and on any safety concerns. List the ideal
properties of pharmaceutical additives.[P6:6-7, 9-10,36 9,11-14,21] . [P6:1-4,
23,36, 5]
A pharmaceutical additive/excipient is defined as any substance (natural,
semisynthetic or synthetic) other than the active drug or prodrug that is
included in the manufacturing process or is contained in a finished
pharmaceutical dosage form.
Classification of additives from regulatory point of view
• First category (approved excipients) : compounds originating from the
food industry (generally recognised as safe or that have been present in
use for a very long time
• Intermediate category (essentially new excipients): compounds obtained
by means of the structural modification of the excipients already
approved or those already used in the food or cosmetic industries.
• Third category : new compounds, never previously used in the
pharmaceutical field and it is growing rapidly due to the present interest
in modified-release formulations and the requirements of the modern
high-productivity compressing/ tabletting machines.
Classification of additives based on origin
• animal (e.g. lactose, gelatin, stearic acid),
• plant (e.g. starches, sugars, cellulose, arginates),
• mineral (e.g. calcium phosphate, silica) and
• synthesis (e.g. PEGs, polysorbates, povidone, etc.)
Pharmaceutical additives must be submitted to more thorough-going
analytical controls guarantee the quality required by the pharmaceutical
industry
Impurities to be kept at an acceptable minimum level esp if they are toxic.
But at times their presence is functionally necessary eg (hemicellulose in
micro-crystalline cellulose.)
“Pure” Excipients that don’t work include
Pure DiCalcium Phosphate doesn’t compact well due to absence of impurity
related crystal defects.
Pure Magnesium Stearate doesn’t lubricate due to absence of water (only
hydrates lubricate)
8

23
Ideal properties of excipients. The ideal excipient should be
1. Nontoxic, Chemically inert (nonreactive with the drug and other
excipients) & Physiologically inert (inert in the human body).
2. Physically & Chemically stable both by itself and in combination with the
drug.
3. Free of unacceptable microbes & does not support mould growth.
4. Colour compatible and maintains the uniformity of shades.(have pleasing
organoleptic properties)
5. Have no deleterious effect on the bioavailability of active drug.
6. able to fill numerous and important functions.
7. Should perform, ie fulfill its inherent function
8. have low equipment and process sensitivity,
9. be well characterized and well accepted by the industry and regulatory
agencies.
A limited choice of excipients with all of these attributes makes formulation
design and excipient selection challenging.

24
Qn No.
in Exam
paper
3.4 Describe the evolution of pharmaceutics in the twentieth century listing any 2
technological breakthroughs. Enumerate the functions (duties) of the hospital
and community pharmacist.
[P3:1-5] [P2A: 25-27, 30-34, 12-16, P2B:1-5]
• The essence of pharmaceutics is the amalgamation of physical science
(physical pharmacy) with aspects of biological science.
• At its center is not only the dosage form with its active and inactive
ingredients but also the behavior of the ensemble in the environment in
which these medicines are used, generally in human subjects.
• From the early days of the 20th century to the mid-1950s, it was
concerned primarily with the science and practice of the manufacture of
medicines (dosage forms) on small and large scales and the preparation of
galenicals.
• Pharmaceutics has progressed as drugs have developed first from natural
product extracts, through synthetic and generally small molecules to
peptides, proteins, and oligonucleotides and DNA itself, into the
beginning era of cell-based therapies.
• Initially not much regard was given to the fate of the dosage form in vivo.
• However, technological break-through led to counter the liabilities of the
inherent drug. E.g.
• 1. Enteric coating of tablets to minimize drug’s irritant effect on the
intestinal mucosa, to minimise degradation of drug by acidic pH.
• 2. The first commercial sustained-release preparations emerged in the late
1940s with the SpansuleTM, which contained wax-coated beads with
different release properties in a soluble capsule, thus controlling release of
the drug in the GI tract.
The day to day duties of a pharmacist varies from one setup to another.
Community pharmacist
– Provide drug information to other healthcare professionals
– Provide patient care by identifying disease, educating patient on disease,
precautions, life style changes, etc
– Runs a business, supervise staff, maintain inventory
– Gather patient information, screen, monitor and advice for self-treatment
with over-the-counter (OTC) products sold without a prescription.
– Prepare doses of Precompounded medication, Extemporaneously
compounded nonsterile medications
8

25
– Dispensing, recordkeeping, and pricing
– receiving a verbal, or oral, prescription in person or by telephone
– preparing the written form of the verbal prescription
– interpreting and evaluating prescriptions
– reviewing patient profile & screen for (e.g., medication history,
duplication of medications, drug interactions, Drug-disease
contraindication, Incorrect dosage or duration of treatment, Drug-
allergy interactions, Clinical abuse/misuse)
– review and discuss with the patient the following
• name and description of medication
• dosage form
• dose
• route of administration
• duration of drug therapy
• action to take after a missed dose
• common severe side effects or adverse effects
• interactions and therapeutic contraindications, ways to prevent
the same, and actions to be taken if they occur
• methods for self-monitoring of the drug therapy
• prescription refill information
• proper storage of the drug
• special directions and precautions for preparation,
administration, and use by the patient
Hospital pharmacist
– Dispenses oral medications
– Prepares and dispenses parenteral medications and doses of
Extemporaneously Compounded Sterile Medications
– Sometimes specializes, with advanced training in an area of patient care
– Educates and counsels patients
– Provides drug information
– Supervise replenishing and transport of controlled drugs for floor stock
– Administers a department by
– developing policies and procedures
– purchasing drugs and supplies
– monitoring drug use in the hospital

26
Qn No.
in Exam
paper
3.5 List the various methods of heating and comment on steam’s benefits and
problems. Using a phase diagram, explain lyophilisation and benefits of freeze
drying.[P11:5-11] [P11:45-47 P11~lyoph.pdf:2-5]
various methods of heating include
• By burning fuels (coal, petroleum, natural gas)
• By Electric heating elements(high resistance)- cheap, clean, rapid
response, easy handling
• Direct heating- material in direct contact with heat (high temperature
achieved, but material must be thermostable)
• Indirect heating- material in contact with a medium or bath, inturn in
contact with heat (controlled temperature achieved) water bath, steam
bath, paraffin-oil bath,
In pharmaceutical processes at anything other than laboratory scale, the most
commonly used heating medium is steam. Steam is also very important as a
sterilizing medium. The reasons for the widespread use of steam include:
• The raw material (water) is cheap and plentiful.
• It is easy to generate, distribute and control.
• It is generally cheaper than viable alternative forms of heating, e.g. electricity.
• It is clean, odourless and tasteless, and accidental contamination of the product
is less likely to be
serious.
• It has a high heat content (in the form of latent heat) and can heat materials
very quickly.
• The heat is given up at a constant temperature, which is useful in controlling
heating processes and in sterilization.
One disadvantage of the use of steam is that it is used at pressures that are
typically two to three times
higher than atmospheric, and thus steam presents potential safety problems and
necessitates the use of
high-strength piping. To appreciate why steam is used in pharmaceutical
processing and the principles of heat transfer using steam it is necessary to
consider how the steam is produced, its heat content, and how the heat content
varies with pressure and temperature.
• The temperature at which water boils depends on the pressure exerted on the
water surface. This is utilized in sterilization processes, where adjustment of the
pressure allows selection of the temperature at which steam condenses and
therefore the temperature at which the articles to be sterilized are exposed.
Similarly, in heat transfer processes, the desired temperature gradient can be
8

achieved by adjusting the steam pressure.
• Problems with Steam contaminated by air
Air is a bad heat conductor and thus reduces heat transfer, increase heating time
and cost. From dalton’s law,
Total Pressure= Partial Pressure(air)+Partial Pressure(steam).
Thus lower pressure means lower steam temperature, lower heat gradient,
higher heating time, possibly poor sterilization.
Freeze drying or lyophilization
• The solution is frozen prior to drying and the solvent is then sublimed
(that is, converted to the gas phase directly from the solid phase), below the
melting point of the solvent.
• Freeze drying is often carried
out under reduced pressure (using a
vacuum pump) to allow drying to
proceed at a reasonable rate.
• This process avoids collapse
of the solid structure, leading to a
low-density, highly porous product
that can quickly reabsorb the solvent
when needed (lyophile means ‘‘likes
the solvent “)
• This method was first used
industrially to produce dehydrated
vaccines, and to bring dehydrated
blood to assist war casualties. It is
regarded as the best method for
preserving the quality and biological
activity of proteins, vitamins, and other bioactive compounds.
• In a typical phase diagram, the boundary between gas and liquid runs
from the triple point to the critical point. Regular drying is shown by the green
arrow; freeze drying, by the blue arrow.
27
by adjusting the steam pressure.
• Problems with Steam contaminated by air
From dalton’s law,
Total Pressure= Partial Pressure(air)+Partial Pressure(steam).
possibly poor sterilization.
Freeze drying or lyophilization
The solution is frozen prior to drying and the solvent is then sublimed
e gas phase directly from the solid phase), below the
melting point of the solvent.
Freeze drying is often carried
out under reduced pressure (using a
vacuum pump) to allow drying to
proceed at a reasonable rate.
This process avoids collapse
structure, leading to a
density, highly porous product
that can quickly reabsorb the solvent
when needed (lyophile means ‘‘likes
This method was first used
industrially to produce dehydrated
vaccines, and to bring dehydrated
ssist war casualties. It is
regarded as the best method for
preserving the quality and biological
activity of proteins, vitamins, and other bioactive compounds.
In a typical phase diagram, the boundary between gas and liquid runs
the critical point. Regular drying is shown by the green
, by the blue arrow.
The solution is frozen prior to drying and the solvent is then sublimed
e gas phase directly from the solid phase), below the
In a typical phase diagram, the boundary between gas and liquid runs
the critical point. Regular drying is shown by the green

28
Lyophilization is a process which extracts the water from foods and other
products so that the foods or products remain stable and are easier to store
at room temperature (ambiant air temperature).
Lyophilization is carried out using a simple principle of physics called
sublimation. Sublimation is the transition of a substance from the solid to the
vapour state, without first passing through an intermediate liquid phase. To
extract water from foods, the process of lyophilization consists of:
1. Freezing the food so that the water in the food become ice;
2. Under a vacuum, sublimating the ice directly into water vapour;
3. Drawing off the water vapour;
4. Once the ice is sublimated, the foods are freeze-dried and can be
removed from the machine.
Lyophilization has many advantages compared to other drying and preserving
techniques.
1. Lyophilization maintains food/ biochemical and chemical reagent
quality because they remains at a temperature that is below
the freezing-point during the process of sublimation; The use of
lyophilization is particularly important when processing lactic bacteria,
because these products are easily affected by heat.
2. Food/biochemicals and chemical reagents which are lyophilized can
usually be stored without refrigeration, which results in a significant
reduction of storage and transportation costs.
3. Lyophilization greatly reduces weight, and this makes the products
easier to transport. For example, many foods contain as much as 90%
water. These foods are 10 times lighter after lyophilization.
4. Because they are porous, most freeze-dried products can be easily
rehydrated. Lyophilization does not significantly reduce volume,
therefore water quickly regains its place in the molecular structure of
the food/ biochemicals and chemical reagents.

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